Metabolism and excretion studies of oral administered naringin, a putative antitussive, in rats and dogs.

Naringin, a major active flavonone glycoside from a traditional Chinese medicine Huajuhong, has been demonstrated to have activities such as peripheral antitussive, mucoregulator and anti-inflammatory. The purpose of this study was to elucidate the metabolism and mass balance of orally administered naringin in rats and dogs. After oral administration of naringin to rats and dogs at doses of 42 mg/kg and 12.4 mg/kg, respectively, metabolites in excreta were identified using a LC-Q-TOF system. The major metabolites including naringin, total naringenin (including free naringenin and its conjugates) and 4-hydroxyphenylpropionic acid in excreta were quantified by a LC-MS/MS system. Twenty-two metabolites were identified in dogs and 17 metabolites were detected in rats. The observed routes of naringin metabolism were hydroxylation, methylation, acetylation, hydrogenation, deglycosylation, dehydrogenation, glucuronidation, sulfation, glucosylation, ring-fission, oxidation, glycine conjugation and dehydroxylation. On the basis of these identified metabolites, a comprehensive metabolic pathway of naringin was proposed. About 21% of administered naringin was recovered in rat excreta in the form of naringin, total naringenin and 4-hydroxyphenylpropionic acid, and about 60% was recovered in dog excreta. The levels of 4-hydroxyphenylpropionic acid in excreta were higher than those of naringin and total naringenin, and the quantified metabolites were excreted more through feces, rather than urine. Most of these metabolites were excreted within 36 h post dose. The results of metabolism and excretion studies provide an explanation for future pharmacological and toxicological findings and are the groundwork for clinical studies.